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PD-1H (VISTA)-mediated suppression of autoimmunity in systemic and cutaneous lupus erythematosus.

Abstract：

:Systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE) of the skin are autoimmune diseases characterized by inappropriate immune responses against self-proteins; the key elements that determine disease pathogenesis and progression are largely unknown. Here, we show that mice lacking immune inhibitory receptor VISTA or programmed death-1 homolog (PD-1H KO) on a BALB/c background spontaneously develop cutaneous and systemic autoimmune diseases resembling human lupus. Cutaneous lupus lesions of PD-1H KO mice have clustering of plasmacytoid dendritic cells (pDCs) similar to human DLE. Using mass cytometry, we identified proinflammatory neutrophils as critical early immune infiltrating cells within cutaneous lupus lesions of PD-1H KO mice. We also found that PD-1H is highly expressed on immune cells in human SLE, DLE lesions, and cutaneous lesions of MRL/lpr mice. A PD-1H agonistic monoclonal antibody in MRL/lpr mice reduces cutaneous disease, autoantibodies, inflammatory cytokines, chemokines, and immune cell expansion. Furthermore, PD-1H on both T cells and myeloid cells including neutrophils and pDCs could transmit inhibitory signals, resulting in reduced activation and function, establishing PD-1H as an inhibitory receptor on T cells and myeloid cells. On the basis of these findings, we propose that PD-1H is a critical element in the pathogenesis and progression of lupus, and PD-1H activation could be effective for treatment of systemic and cutaneous lupus.

journal_name

Sci Transl Med

journal_title

Science translational medicine

authors

Han X,Vesely MD,Yang W,Sanmamed MF,Badri T,Alawa J,López-Giráldez F,Gaule P,Lee SW,Zhang JP,Nie X,Nassar A,Boto A,Flies DB,Zheng L,Kim TK,Moeckel GW,McNiff JM,Chen L

doi

10.1126/scitranslmed.aax1159

subject

Has Abstract

pub_date

2019-12-11 00:00:00

issue

522

eissn

1946-6234

issn

1946-6242

pii

11/522/eaax1159

journal_volume

11

pub_type

杂志文章

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